Selective Inhibition on RAGE-binding AGEs Required by Bioactive Peptide Alpha-S2 Case in Protein from Goat Ethawah Breed Milk: Study of Biological Modeling.
Selective Inhibition on RAGE-binding AGEs Required by Bioactive Peptide Alpha-S2 Case in Protein from Goat Ethawah Breed Milk: Study of Biological Modeling.
复制标题
对果阿果阿特牛奶的蛋白质生物活性肽α-S2病例所需的对愤怒结合年龄的选择性抑制：生物建模研究。
DOI：
10.5455/aim.2015.23.90-96
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Widodo N
中科院分区：
文献类型：
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作者：
Fatchiyah F;Hardiyanti F;Widodo N
晚期糖基化终产物（AGE）在糖尿病、心血管疾病、中风、神经病和肾病等多种退行性疾病的发生发展中起着关键作用。已经进行了不同的研究，将AGEs用作疾病治疗的药物靶点。在前期的研究中，我们从Ethawah羊奶中发现了具有抗糖尿病作用的活性肽，其作用机制可能是通过抑制AGE受体的功能来实现的。然而，活性肽抑制AGE-AGE受体结合的机制尚不清楚.因此，我们利用分子对接技术，通过计算多肽、AGEs和底物之间的结合势能，研究了AGEs的抑制机制。通过SWISS-MODEL Web服务器进行三维结构预测建模。利用HEX 8.0、Pymol和Discovery Studio 4.0软件，通过对接系统对虚拟交互进行分析。该研究表明AGEs（Argypiridine、Imidazole、Pentosidine和Pyrraline）结合到P160的C-结构域。测得其与Argypirimidine、Imidazole、Pentosidine和Pyrraline的结合能分别为378.35kJ/mol、-74.57kJ/mol、-301.25kJ/mol和-400.72kJ/mol。从Ethawah羊奶中提取的8种肽中，我们发现了3种肽，它们分别是CSN 1 S2 f41-47、CSN 1 S2 f182-189和CSN 1 S2 f214-221。精氨酸残基47处的CSN 1 S22 f41-47与丝氨酸的脯氨酸162、亮氨酸163和亮氨酸158相互作用。CSN 1 S2 f41-47、CSN 1 S2 f182-189和CSN 1 S2 f214-221与β-环糊精的总结合能分别为-378.35kJ/mol、-359.97kJ/mol和-356.78kJ/mol。总结合能和结合模式表明，AGEs更倾向于与肽结合，阻断AGEs与AGEs功能位点的结合。进一步分析表明，复合肽-β使AGE的结合位点在功能结构域β上发生了移动。本研究表明，来自Ethawah羊奶的肽可能作为AGEs-β-淀粉样蛋白相互作用的抑制剂，在细胞水平上损害信号转导级联。
Advanced Glycation End Products (AGE) play a pivotal role in the development various degenerative diseases such as diabetes, cardiovascular disease, stroke, neuropathy, and nephropathy. Different studies have been done to employ AGEs as drug targets for the diseases therapy. In previous study, we have found bioactive peptide from Ethawah goat milk for anti-diabetic that may work through inhibition of AGE receptor function. However, the mechanism of bioactive peptides inhibits AGE- AGE receptor (RAGE) bonding still not clear yet. Therefore we investigated the inhibition mechanism by calculate the potential energy binding among the peptides, AGEs and RAGE using molecular docking system. Modeling 3D-structure was predicted by SWISS-MODEL web server. The virtual interaction was analyzed by docking system using HEX 8.0, Pymol and Discovery Studio 4.0 software. this study showed that AGEs (Argypirimidine, Imidazole, Pentosidine and Pyrraline) bind to C-domain of RAGE. The total energy binding of RAGE with Argypirimidine, Imidazole, Pentosidine and Pyrraline were 378.35kJ/mol, -74.57kJ/mol, -301.25kJ/mol and -400.72kJ/mol, respectively. We have found three peptides among eight peptides from Ethawah goat milk, which are able bind to C-domain of RAGE, there are CSN1S2 f41-47, CSN1S2 f182-189, and CSN1S2 f214-221. The CSN1S22 f41-47 at arginine residue 47 interacts with proline162, leusine163 and leusine158 of RAGE. The total binding energy between CSN1S2 f41-47, CSN1S2 f182-189, and CSN1S2 f214-221 with RAGE were -378.35 kJ/mol, -359.97kJ/mol, -356.78 kJ/mol, respectively. Total binding energy and binding pattern indicated that RAGE more prefer bind with peptide and block AGE bind to functional site of RAGE. Further analysis showed that complex peptide-RAGE shifted binding site of AGE on function domain RAGE. This study suggested that the peptides from Ethawah goat milk may act as an inhibitor of AGEs-RAGE interaction that impaired signal transduction cascade at the cellular level.